MDR1 MULTI-DRUG RESISTANCE

Below is the beginning of some information on MDR1 gene mutation found on Australian Shepherd Health & Genetics web site. Otis our male has 1 copy of this gene. We want to help everyone to understand this mutation and how it may effect a dog with MDR1. THE EASIEST WAY TO HELP UNDERSTAND THE ISSUES A DOG HAS WITH MDR1, IS TO CONSIDER THAT THE DOG IS ALLERGIC TO CERTAIN DRUGS. We have all our pups from Otis tested so you will know whether they have MDR1 gene before you buy a pup. Otis is a sound sire with good confirmation. 1 in every 2 Australian shepherds have this mutation. We have found that the only concerns we have is the type of worm prevention we use and anti diarrhea drugs we use. When we go to vet for treatment of any kind that we need to make sure the vet is aware that he is a carrier of 1 copy of the MDR1 gene. If they have surgery the vet will lower the dose so has to not put the dog in danger. Also you need to make sure the drugs used for treatment safe for dogs with MDR1 gene. 1 copy of the gene is all the pups we have could get has the mother doesn't have this gene . Pups with 2 copies are in more danger of reactions then those with just one . Please check out the information below and the link to the web site Australian Shepherd Health & Genetics Institute.

What is MDR1?

MDR1 is the abbreviated name of a gene called Multi-Drug Resistance 1. A mutation of this gene causes sensitivity to Ivermectin and a number of other drugs. Dogs with the mutation will react to those drugs. Whether a dog reacts depends on the dosage of the drug. A dog may not react to very low doses, as with the amount of Ivermectin found in heart worm products. Typical doses of a variety of medications will cause reactions in dogs with two copies of the mutation, but some drugs – most notably several chemotherapy agents – can cause reactions in dogs with only one. Dogs with this mutation have a transport defect—the drug goes in to their brains, fails to be transported out, and builds up to toxic levels. This causes serious neurological problems including seizures and sometimes death.

Australian Shepherds, along with several other mostly collie-type breeds, can carry a genetic mutation that makes them sensitive to certain drugs. Use of those drugs can cause serious neurological illness or death.

Fortunately, there is a DNA test that will let you know whether your dog has this mutation. All you have to do is provide a cheek swab. It isn’t even necessary to go to the vet. for more infromation on MDR1 please read more at Australian Shepherd Health & Genetics Institute

Which drugs should I be concerned about?

Many different drugs and drug classes have been reported to cause problems in dogs with the MDR1 mutation. Drugs that have been documented to cause reactions include:

Ivermectin (antiparasitic agent) While the dose of ivermectin used to prevent heartworm infection is safe in dogs with the mutation (6 micrograms per kilogram), higher doses, such as those used for treating mange (300-600 micrograms per kilogram), will cause neurological toxicity in dogs that are homozygous for the MDR1 mutation (MDR1 mutant/mutant) and can cause toxicity in dogs that are heterozygous for the mutation (MDR1 mutant/normal).
Eprinomectin (antiparasitic agent) Cats with the MDR1 mutation have experienced severe neurological toxicity and death after being treated with a monthly heartworm preventive containing eprinomectin. In contrast to dogs, these adverse effects occurred when the product was used at the manufacturer’s recommended label dose.
Selamectin, milbemycin, and moxidectin (antaparasitic agents) Similar to ivermectin, these drugs are safe in dogs with the mutation if used for heartworm prevention at the manufacturer’s recommended dose. Higher doses (generally 10-20 times higher than the heartworm prevention dose) have been documented to cause neurological toxicity in dogs with the MDR1 mutation.
Loperamide (ImodiumTM; antidiarrheal agent) At doses used to treat diarrhea, this drug will cause neurological toxicity in dogs with the MDR1 mutation. This drug should be avoided in all dogs with the MDR1 mutation.
Acepromazine (tranquilizer and pre-anesthetic agent) Dose reductions are required for dogs MDR1 mutant/mutant and MDR1 mutant/normal.
Butorphanol (analgesic and pre-anesthetic agent) Dose reduction required for dogs MDR1 mutant/mutant and MDR1 mutant/normal.
Chemotherapy agents (Vincristine, Vinblastine, Doxorubicin, Paclitaxel) Dose reductions are required for dogs MDR1 mutant/mutant and MDR1 mutant/normal to avoid severe toxicity.
Apomorphine This drug is used to induce vomiting in dogs that have ingested poisons/toxins. It can cause central nervous system depression in dogs with the MDR1 mutation at standard doses.
The information here on drugs is from Washington State University and there web site and is not a complete list please check with your veterinarian for more information